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• W97053298 abstract "ABSTRACT We have prepared molecular clones of an entire provirus of mouse mammary tumor virus (MMTV) and of the unoccupied integration site for this provirus in rat cell DNA in order to study the organization of interesting regions of viral DNA and the mechanisms of integration and transcriptional control. The provirus fortuitously lacks an apparently unclonable region of the MMTV genome as well as the single Eco RI site present in wild type proviruses; however, it includes both copies of a large direct repeat (ca. 1300 nt) present at the ends of all MMTV proviruses, and it is expressed and regulated by glucocorticoid hormones in the infected rat cell. Sequencing studies of the relevant regions of the cloned DNA's show that the large units of directly repeated DNA include a short (6 nt) inverted repeat at their termini. The provirus is flanked by a 5 or 6 nt direct repeat apparently generated by duplication of a host sequence during integrative recombination, since this sequence is present only once in the unoccupied integration site. In addition, one or two nucleotide pairs predicted to be at the right hand end of viral DNA are missing from the provirus, implying loss at some stage subsequent to DNA synthesis. We have also identified proviral sequences within the large terminal repeats likely to serve as signals for synthesis and processing of viral RNA and other sequences adjacent to the repeat units involved in the priming of minus and plus strands of viral DNA. Our findings, in concert with recent work in a number of laboratories, suggest that the replication of retroviruses involves the use of direct and inverted repetitions at several stages: the RNA genome is diploid, and each subunit bears short direct repeats; the linear double-stranded product of reverse transcription carries long direct terminal repeats composed of sequences unique to both the 3′ and 5′ ends of viral RNA; these terminal repeat units are concluded with short inverted repeats; closed circular DNA contains either one or two copies of the large direct repeats; integrated (proviral) DNA is co-linear with unintegrated linear DNA, including both copies of the large repeat unit; and the integration events duplicate a short sequence of host DNA which forms a direct repeat flanking the provirus. Although the functional implications of these designs are not fully understood, the provirus bears a striking structural relationship to transposable elements of bacteria and other organisms, and the repeated sequences seem likely to be instrumental in viral DNA synthesis, integration, and the control of transcription and processing of viral RNA." @default.
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• W97053298 date "1980-01-01" @default.
• W97053298 modified "2023-09-27" @default.
• W97053298 title "LEARNING ABOUT THE REPLICATION OF RETROVIRUSES FROM A SINGLE CLONED PROVIRUS OF MOUSE MAMMARY TUMOR VIRUS" @default.
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• W97053298 doi "https://doi.org/10.1016/b978-0-12-255850-4.50027-5" @default.
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